Pharmacology of Antidepressants and Mood Stabilisers

Question 1

What are the clinical uses of antidepressants?

Answer 1

• Moderate to severe depression
• Dysthymia
• Generalised anxiety disorder
• Panic disorder, OCD, PTSD
• Premenstrual dysphoric disorder
• Bulimia nervosa
• Neuropathic pain

Question 2

Name 3 groups of antidepressant drugs.

Answer 2

• Monoamine oxidase inhibitors.
• Monoamine reuptake inhibitors.
• Atypical drugs (post-synaptic receptor effects).

Question 3

Give 3 subgroups of monoamine reuptake inhibitors.

Answer 3

• Tricyclics.
• Other non-selective reuptake inhibitors.
• Selective serotonin reuptake inhibitors.

Question 4

SSRI’s belong to what group?

Answer 4

Monoamine reuptake inhibitors

Question 5

How many amine groups do monoamines have?

Answer 5

1 lol obvs

Question 6

How do most antidepressants work?

Answer 6

By altering monoamine neurotransmission in some way

Question 7

What does depression result from?

Answer 7

A functional problem in the monoamine transmitters

Question 8

Name 3 main monoamine transmitters.

Answer 8

• Serotonin (5-HT)
• Noradrenaline
• Dopamine

Question 9

What do drugs that deplete stores of monoamines do?

Answer 9

Cause a low mood

Question 10

CSF from depressed patients have reduced levels of monoamines or metabolites

Answer 10

TRUE

Question 11

Most drugs that treat depression act to ________ monoaminergic transmission

Answer 11

INCREASE

Question 12

What is the life cycle of serotonin?

Answer 12

1. Tryptophan is in the presynaptic cleft
2. It is converted to 5-OH-tryptophan by tryptophan hydroxyls (enzyme)
3. 5-OH-tryptophan is converted to 5-HT by LAA-decarboxylase (enzyme)
4. 5-HT leaves presynaptic cleft and is taken up by postsynaptic cleft
5. 5-HT is then re-taken by presynaptic cleft
6. 5-HT converted to 5-HIAA by MAO’s

Question 13

What is the life cycle of noradrenaline?

Answer 13

1. Tyrosine in presynaptic cleft
   2 Tyrosine converted to DOPA by tyrosine hydeoxylase (enzyme)
2. DOPA converted to DA by LAA-decarboxylase (enzyme)
3. DA converted to NA by DA-beta-hydroxylase (enzyme)
4. NA leaves presynaptic cleft and is taken up by postsynaptic cleft
5. NA is then re-taken by presynaptic cleft
6. NA converted to MHPG by MAO’s

Question 14

Name 2 MAO inhibitors.

Answer 14

• Phenelzine

* Moclobemide

Question 15

How to MAO inhibitors work?

Answer 15

Inhibit MAO to increase neurotransmitter concentration.

Question 16

What is the mode of action of MAO inhibitors?

Answer 16

Either irreversible or reversible inhibitors of MAO-A and B

Question 17

Which MAO inhibitor is reversible and what one is irreversible?

Answer 17

Irreversible – phenelzine.

Reversible – moclobemide.

Question 18

What are the main side effects of MAO inhibitors?

Answer 18

• ‘Cheese reaction’/Hypertensive crisis.
• Potentiates effects of other drugs (ie. barbiturates) by decreasing their metabolism.
• Insomnia.
• Postural hypotension.
• Peripheral oedema.

Question 19

What is the ‘cheese reaction’/hypertensive crisis caused by?

Answer 19

Inhibition of MAO-A in the gut (+ liver) by irreversible inhibitors, preventing breakdown of dietary tyramine, and by multiple drugs that potentiate amine transmission (ie. pseudoephedrine, other anti-depressants).

Question 20

To prevent hypertensive crisis, what should patients be advised?

Answer 20

Don’t eat cheese or gravy :(

Question 21

How do tricyclic antidepressants work?

Answer 21

Block the re-uptake of NT

Question 22

Give 4 examples of TCA’s.

Answer 22

Imipramine.
Dosulepin.
Amitriptyline.
Lofepramine.

Question 23

What is the mode of action of TCA’s?

Answer 23

Block the reuptake of monoamines (mainly noradrenaline and 5-HT) into presynaptic terminals.

Question 24

What are the common side effects of TCA’s?

Answer 24

• Anticholinergic-
  blurred vision, dry mouth, constipation, urinary retention
• Sedation
• Weight gain
• Cardiovascular-
  Postural hypotension, tachycardia, arrhythmias
• Cardiotoxic in overdose

Question 25

Give 4 examples of SSRI's.

Answer 25

* Fluoxetine. * Citalopram/Escitalopram. * Sertraline. * (Paroxetine)

Question 26

What is the mode of action of SSRI's?

Answer 26

Selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft

Question 27

What are the common side effects of SSRI's?

Answer 27

* Nausea * Headache * Sweating / vivid dreams * Worsened anxiety * Sexual dysfunction * Hyponatraemia (in elderly) * Transient increase in self-harm / suicidal ideation in <25 years

Question 28

Name 2 dual reuptake inhibitors (SNRI's).

Answer 28

* Venlafaxine | * Duloxetine

Question 29

How do SNRI's work?

Answer 29

Block the reuptake of monoamines (noradrenaline AND 5-HT) into presynaptic terminals

Question 30

What are the side effects of SNRI's? What is the main advantage to the use of these?

Answer 30

S/E’s are similar to SSRI’s Lack major receptor-blocking actions so fewer side effects than tricyclics

Question 31

Mirtazapine

Answer 31

Has mixed receptor affects

Question 32

What does Mirtazapine block?

Answer 32

alpha2, 5-HT2 & 5-HT3

Question 33

What are the side effects of a drug like mirtazapine which has mixed receptor effects?

Answer 33

Weight gain + sedation

Question 34

What can mirtazapine do if given with SSRI’s?

Answer 34

Block serotonergic side-effects. | ie. nausea  5-HT3 antagonists are used as anti-emetics.

Question 35

Name a dopamine uptake inhibitor.

Answer 35

Bupropion.

Question 36

What is the onset of action like in most antidepressants?

Answer 36

Delayed - several weeks

Question 37

There is clearer evidence for the usefulness of antidepressants in what?

Answer 37

More severe depression  large placebo response in mild depression

Question 38

Who should you be cautious of the use of antidepressants in? Why?

Answer 38

Young adults/teenagers due to transient increase in suicidal/aggressive ideas

Question 39

What is lithium for bipolar normally given as?

Answer 39

Lithium carbonate

Question 40

Different forms of lithium have different bioavailability so be careful about doses if the type of lithium salt is changed

Answer 40

WARNING

Question 41

What must be monitored with lithium? Why?

Answer 41

12-hour post-dose blood levels. | - because of narrow therapeutic index.

Question 42

What are the common side effects of lithium?

Answer 42

* Dry mouth / strange taste * Polydipsia & polyuria * Tremor * Hypothyroidism * Long term reduced renal function * Nephrogenic diabetes insipidus * Weight gain

Question 43

What are the toxic effects of lithium?

Answer 43

* Vomiting * Diarrhoea * Ataxia / coarse tremor * Drowsiness * Convulsions * Coma

Question 44

Give examples of anticonvulsant drugs which can be used in long term treatment of BPAD.

Answer 44

* Valproic acid. * Lamotrigine. * Carbamazepine

Question 45

What are the side-effects of carbamazepine?

Answer 45

Drowsiness, ataxia, cardiovascular effects, induces liver enzymes

Question 46

What is the main issue surrounding valproate?

Answer 46

Teratogenicity – neural tube defects Therefore, don’t give to women of child-bearing age.

Question 47

Give 4 examples of antipsychotics that can be used as mood stabilisers.

Answer 47

* Quetiapine. * Aripiprazole. * Olanzapine. * Lurasidone.

Question 48

What is the role of antipsychotics?

Answer 48

Dopamine + 5-HT antagonism

Question 49

What side effects may be associated with antipsychotics?

Answer 49

* Sedation, weight gain, metabolic syndrome | * Extra-pyramidal side-effects (aripiprazole)

Question 50

What 5 things are involved in the serotonin pathway of the brain?

Answer 50

* Mood * Sleep * Feeding * Behaviour * Sensory perception